Pipette apparatus

ABSTRACT

A manually-operated pipette for handling small volumes of liquid includes a spring-biased plunger and volume rod extending into a volume chamber. A spring-biased overriding slide sleeve is coupled to the plunger only during overriding ejection motion of the plunger, and switch means coupled to the sleeve provides electrical signalling of the ejecting motion. A removable universal disposable tip for pipettes of various maximum capacities communicates with the volume chamber of the body.

[451 Sept. 11, 1973 m W a W. S W

Waited Heller et al.

3,343,539 9/1967 Moorhouse.................... 3,498,135 3/1970 Seitzboth of Santa Rosa Cahf' Primary Examiner-S. Clement Swisher [73]Assignee: Heller Laboratories, Santa Rosa, Attorney-A. C. Smith Calif.

[57] ABSTRACT A manually-operated pipette for handling small vol- 22Filed: Sept. 15, 1971 [21] Appl. No.: 180,814

only during overriding ejection motion of the plunger,

[51] lint.

[58] Field of Search 73/4254 P, 425.6; and switch means coupled to thesleeve provides electrical signalling of the ejecting motion. Aremovable universal disposable tip for pipettes of various maximumcapacities communicates with the volume chamber of the body.

[56] References Cited UNITED STATES PATENTS 73/425.6 4 Claims, 2 DrawingFigures LIQUID Patented Sept. 11, 1973 3,757,585

2 Sheets-Sheet l ||I U: t] E: 63 u I il/25 INVENTORS ROBERT E. HELLERSTANLEY T. HALL Patented Sept. 11, 1973 2 Sheets-Sheet 2 INVENTORSROBERT E. HELLER STANLEY T. HALL igure 2 IIWETTE APPARATUS BACKGROUND OFTHE INVENTION generally performed in conventional pipettes at an inexactposition of the ejection stroke, thereby creating inaccuracies in thetiming of external events with respect to the complete ejection of avolume of liquid.

SUMMARY OF THE INVENTION In accordance with the illustrated embodimentof the present invention a spring-biased plunger protrudes from the bodyof a pipette for convenient manual actuation. A sliding volume rodattached to the plunger protrudes through a seal into a volume chamberwithin the body for altering the volume thereof to draw up or ejectliquid in response to manual actuation of the plunger. A sleeve isslidably disposed within the body to engage the plunger only duringfinal movement thereof in an ejection cycle and a switch is actuated bythe sleeve to electrically signal external equipment at a preselectedplunger position in the ejection cycle. A

' disposable tip with calibration marks to provide a visual cross checkattaches to the body in communication with the volume chamber to containa measured volume of liquid within the tapered internal bore of the tip.

DESCRIPTION OF THE DRAWINGS FIG. 1 is a sectional view of the pipetteand disposable tip of the present invention in rest position at thestart of an ejection cycle; and

FIG. 2 is a sectional view of the pipette and disposable tip of FIG. 1showing the sleeve means actuated by the plunger during overridingejection operation. FIG. 2 also shows means for actuation of electricalcontacts.

DESCRIPTION OF THE PREFERRED EMBODIMENT Referring now to FIG. 1, thereis shown a generally cylindrical body 9 having diametrically opposedlateral extensions 11 protruding therefrom near the top portion of thebody. These lateral extensions 11 serve as a convenient finger gripduring operation of the pipette. Within the body 9 is a generallyinternal bore 13 which extends down from the upper end of the body 15 toa shoulder 17 at the base of the internal bore 13. A plunger 19 includesa volume rod 21 attached thereto which is disposed to move axiallywithinthe internal bore 13 in response to manual pressure applied to thebutton or knob 23 attached to the upper end of the plunger 19. The body9 connects to a volume cylinder 25 which is threaded into body 9 andwhich includes a volume chamber 27 into which protrudes the volume rod21. Between the internal bore 13 and the volume chamber 27 within thebody 9 and volume cylinder 25, there is disposed an O-ring seal 29 whichslidably engages the outside diameter of the volume rod 21 to form anairtight or gastight seal between the body and the volume rod 21. TheO-ring seal 29 also seals chambers 13 and 27 from each other and sealsthem from external atmosphere at the point of joining. Thus, in responseto pressure manually applied to the button 23 of the plunger 19, thevolume rod 21 is urged through the seal 29 into the volume chamber 27 toalter the volume therewithin and thereby to produce the air or gasdisplacing action of the pipette. This air or gas displacement willdisplace a like volume in pipette tip 51 which is joined to volumecylinder 25 in an airtight or gastight tapered seal. On the return, orintake stroke, the volume rod 21 is withdrawn from the volume chamber 27to draw air or gas into the chamber 27 through the inlet 28. Therefore,if the pipette is held with the tip 51 down and placed into a liquid,said liquid will be drawn into disposable tip 51. However, the design issuch that no liquid is drawn through inlet 28 and into volume chamber 27or any other portion of the pipette. All liquid remains in the tip whichis diposed of after the measurement is completed.

It has been found that the outside diameter of a rod such as volume rod21 may be held to closer tolerances than the internal diameter of acylindrical bore such as that within the volume chamber 27. For thisreason, the volume rod is used as the calibrating device in thispipette, its diameter being a critical measurement. Thus, the internaldimensions of volume chamber 27 need not be critically maintained butneed only provide adequate clearance to permit slidable movement of thevolume rod 21 within the volume chamber 27 without unnecessary air spacearound the rod. Thus, with the 0-ring seal 29 slidably engaged about thediameter of volume rod 21, the air or gas displacement volume of thepresent pipette is accurately controlled in response to movement of thevolume rod into the volume chamber 27. This air or gas displacement willdisplace a like volume of liquid in pipette tip 51 with an accuracycomparable to the calibration accuracy of the volume rod.

The plunger 19 and volume rod 21 are resiliently biased away from theshoulder 17 of the internal bore 13 by a first coil spring 31 which ispositioned about the volume rod 21 within the internal bore 13. Thisspring 31, which bears against a shoulder 33 of the plunger 19, urgesthe plunger 19 into normal position outwardly protruding from the body 9and biased against retainer plate 35. This plate is attached to theupper end of the body 9 by screws 34 and 36, and spans the laterallyprotruding elements 11 to protect the internal elements. Also containedwithin the internal bore 13 of the body 9 is a sleeve 37 which isdisposed to slide axially within internal bore 13 and which is biasedaway from the shoulder 17 by a second spring 39. Thus, the springs 31and 39 which bear against the shoulder 17 ofv internal bore 13 extendcoaxially over a common portion of their lengths and serve toresiliently bias both the plunger 19 (and volume rod 21 attachedthereto) and the sleeve 37. The coextension of springs over the commonportion of their respective lengths thus reduces the over-all axiallength of the pipette'of the present invention and thus facilitates easeof use and handling.

Referring now to FIG. 2, the plunger and volume rod 19, 21 are shown inposition beyond the maximally depressed position and are shown in theejection override position with the lower shoulder33 of plunger 19engaged with the inwardly extending shoulder 41 carried by sleeve 37. Itshould be noted that, in this position, the plunger 1? is engaged withthe sleeve 37 and manually applied pressure to the button 23 at the topend of plunger 19 must thus overcome the spring forces produced by boththe spring 31 and the spring 39. This provides a measure of tactilefeedback to the operator which indicates to him that the pipette hasbeen operated beyond the calibrated range of displacement volume and isin the override or blowout portion of the ejection cycle. Thus, acalibrated volume of liquid is determined by movement of the plunger 19and volume rod 21 (against the lightly spring-biased force provided byspring 31) from the rest position in which shoulder 33 of plunger 19rests on the retainer plate 35 to the position at which the shoulder 33on plunger 19 engages shoulder 41 on sleeve 37. The abrupt increase inthe required force to depress sleeve 37 with plunger 19 thus provides apositive-feeling indication of the completion of the calibrated portionof the ejection cycle and alerts the operator to the initiation of theblowout" cycle which permits the volume rod 21 to override itsspring-biased stop position (provided by sleeve 37) and carry both theplunger 19, volume rod 21 and sleeve 37 into the override or blowout"portion of the ejection cycle. This overriding motion of the volume rod21 assures complete ejection of liquid drawn up into the volume pipettetip 51 during the intake cycle of operation of the plunger.

The overriding motion during the ejection cycle causes sleeve 37 toactuate switch 43 contained within one of the lateral extensions 11 ofthe body 9. This switch may contain a pair of resilient metal springleaves which are spaced apart out of electrical contact during normalposition of the sleeve 37 against the retainer plate 35. One spring leaf45 is positioned to be actuated by the sliding movement of the sleeve37, thereby to contact the other spring leaf 47 of the switch means 43.Electrical connections to suitable external circuitry such as timer,mixers, heaters, coolers, or the like may be made through conventionalelectrical jack connector 49 which connects to the spring leaves 45 and47 as shown. Thus, the switch means 43 arranged within the body 9 of thepresent pipette is actuated only in response to overriding movement ofthe sleeve during the uncalibrated blowout portion of the ejectioncycle, which occurs only after completion of the calibrated ejectioncycle. This assures that electrical signalling of external circuitry maybe performed only during the ejection cycle and only upon completeexpulsion of the calibrated volume of liquid. This eliminates thepossibilities of premature electrical signalling of external circuitryas the liquid is being drawn up or during the ejection cycle when only aportion of the liquid being handled has been ejected, a problem commonlyencountered in conventional pipettes.

The pipette system for liquid-handling includes both the volume chamber27 located within the lower body portion 25 and a disposable tip 51attached thereto. In order to avoid contamination of the volume chamberof the pipette, it is common practice to handle the liquid entirelywithin the disposable tip 51. For this reason, the tip 51 may beconveniently formed inexpensively of a suitable material such as atranslucent plastic. The tip 51 includes an orifice 53 at its distal endremotely from the connector port or attachment end 55 and includes atapered internal bore 57 through the tip which communicates with boththe orifice 53 and the connector port 55. The internal bore 57 is formedat two taper angles over the length of the tip. The first taper angle 59adjacent the orifice 53 may be of the order of five degrees and extendsover approximately forty to fifty percent of the length of the tip 51.The second taper angle 61 extends over the remaining portion of thelength of the tip 51 and is of smaller angle (typically one and one-halfdegrees) than the first taper angle 59. The tip 51 constructed in thismanner may thus serve as a universal, disposable tip capable of handlinga wide range of liquid volumes. In addition, the external surface of thetip 51 includes volumetric graduations 63 disposed at selected locationsaway from the orifice 53. These volumetric graduations may be in theform of abrupt transitions in the external diameter of the tip or may begouged or scored or otherwise marked into the outside surface of the tip51. These volumetric graduations may thus provide a continuing visualcross check on the accuracy of the pipette of the present invention.

The maximum volumetric capacity of these pipettes may be alteredconveniently simply by altering the diameter and/or length of stroke ofthe volume rod 21, the associated O-ring seal 29, and the volume chamber27 within the volume cylinder 25. Pipettes of smaller maximum capacitymay thus have volume cylinders of smaller external diameter.Specifically, the external diameter and length of the end of the volumecylinder 25 is selected to protrude into the tapered internal bore 57 oftip 51 to a position slightly above volumetric graduation 63 whichrepresents the calibrated volume of the pipette attached to the tip.This enhances the universal application of the same tip design for usewith a wide range of pipettes of widely varying maximum capacities. Foreach size of pipette, the end of the volume cylinder 25 thus press fitsinto the tapered bore 57 of the tip at a position approximately one-halfdivision above its appropriate volumetric graduation. Each volumetricgraduation indicates the actual maximum capacity of the volume chamberand volume rod 21, 27 of the appropriate size pipette. This provides avisual cross check on the accuracy of the pipette since the maximumcapacity of calibrated volume should correspond with the next volumetricgraduation visible beyond the end of the volume cylinder 25 positionedwithin the internal bore 57. This significantly reduces the excess airvolume within the liquid-carrying chamber, prevents meniscus bounce andthereby preserves the accuracy of the calibrated liquid-handlingcapacity. A complete line of pipettes of different maximum capacities,having color-coded markings on band 30 and plunger buttons 23, may thusbe used with one size of tip 51 of the present invention. Other pipettesusually use several sizes of tip to accommodate different-sized pipettesand to avoid the cushioning problem caused by measuring a small volumeof liquid within a relatively large pipette tip.

We claim:

1. Pipetting apparatus comprising:

a body including an internal bore therein having a shoulder located at aselected depth within the internal bore, the body having a narrowingportion comprising a volume cylinder which is hollowed to fonn a volumechamber which is axially spaced away from said body internal bore andwhich communicates with said internal bore through an axially alignedaperture within the body;

sleeve means mounted within said body for slidable movement therewithinin a direction substantially along the axis of said internal bore;

a plunger including a volume rod attached thereto mounted within saidbody for slidable movement therewithin with said plunger slidablymovable within said internal bore and with said volume rod protrudingthrough said aperture into said volume chamber;

coupling means between said plunger and said sleeve means for engagingthe sleeve means to slide with said plunger within said body only over apreselected nearer portion of the slidable movement of the plunger whichis near the shoulder of the internal bore and for disengaging the sleevemeans from said plunger over a remaining portion of the slidablemovement of said plunger which is remote from said shoulder;

first spring means disposed within said body for resiliently biasingsaid plunger away from said shoulder;

second spring means disposed within said body to resiliently bias saidsleeve means with respect to said body for yieldably maintaining saidsleeve means in fixed position of disengagement from the plunger duringsaid remaining remote portion of slidable movement thereof; and

electrical switch means disposed within said body to be actuated inresponse to sliding movement of said sleeve means with said plungerduring said preselected nearer portion of the movement thereof.

2. Pipetting apparatus as in claim 1 wherein:

said plunger includes a manually-actuatable push rod coupled thereto toprotrude from the end of said body remote from said shoulder insubstantially coaxial alignment with said plunger; 1

said body includes substantially diametrically opposed, laterallyextending portions near the end of the body from which said push rodprotrudes; and

said switch means is supported within a laterally extending portion ofthe body to be actuated by sliding movement of said sleeve means withinsaid internal bore of the body.

3. Pipetting apparatus comprising:

a body including an internal bore therein having a shoulder located at aselected depth within the internal bore, the body having a narrowingportion comprising a volume cylinder which is hollowed to form a volumechamber which is axially spaced away from said body internal bore andwhich communicates with said internal bore through an axially alignedaperture within the body; v

sleeve means mounted within said body for slidable movement therewithinin a direction substantially along the axis of said internal bore;

a plunger including a volume rod attached thereto mounted within saidbody for slidable movement therewithin with said plunger slidablymovable within said internal bore and with said volume rod protrudingthrough said aperture into said volume chamber;

coupling means between said plunger and said sleeve means for engagingthe sleeve means to slide with said plunger within said body only over apreselected nearer portion of the slidable movement of the plunger whichis near the shoulder of the internal bore and for disengaging the sleevemeans from said plunger over a remaining portion of the slidablemovement of said plunger which is remote from said shoulder;

first spring means disposed within said body for resiliently biasingsaid plunger away from said shoulder;

second spring means disposed within said body to resiliently bias saidsleeve means with respect to said body for yieldably maintaining saidsleeve means in fixed position of disengagement from the plunger duringsaid remaining remote portion of slidable movement thereof;

a liquid-holding tip for said apparatus having a tapered internal borewhich communicates with an orifice at the narrow end of the tip and witha connection port at the wide end within which the distal end of thevolume cylinder is inserted;

said tip includes volumetric graduations thereon for visually measuringa volume of liquid within the region of the internal tapered borethereof adjacent said orifice; and

the extreme outside lateral dimension of the volume cylinder near thedistal end thereof corresponds with the internal dimension of thetapered bore in said tip for sealingly engaging the internal taperedbore of said tip above and proximate the volumetric graduation that isrepresentative of said volume rod protruding into said volume chamber bythe amount of the calibrated portion of slidable movement of saidplunger.

4. A universal liquid-holding tip adapted to attach to the inlet anddischarge ends of pipetting apparatus having end diameters that arerepresentative of the maximum capacities of the pipetting apparatus, thetip comprising:

an elongated vessel having an internal bore which communicates with anddiverges from an orifice at the narrow end of the vessel and which alsocommunicates with a connection port at the wide end of the vessel, saidelongated vessel having volumetric graduations thereon from the orificeend thereof corresponding substantially to the maximum capacities ofpipetting apparatus to be associated therewith; and

the divergence of the internal bore providing sealing engagement withthe end of associated pipetting apparatus at adepth within the internalbore that substantially corresponds with a volumetric graduation for aliquid volume in the region adjacent the orifice which is not less thanthe maximum capacity of the associated pipetting apparatus.

1. Pipetting apparatus comprising: a body including an internal boretherein having a shoulder located at a selected depth within theinternal bore, the body having a narrowing portion comprising a volumecylinder which is hollowed to form a volume chamber which is axiallyspaced away from said body internal bore and which communicates withsaid internal bore through an axially aligned aperture within the body;sleeve means mounted within said body for slidable movement therewithinin a direction substantially along the axis of said internal bore; aplunger including a volume rod attached thereto mounted within said bodyfor slidable movement therewithin with said plunger slidably movablewithin said internal bore and with said volume rod protruding throughsaid aperture into said volume chamber; coupling means between saidplunger and said sleeve means for engaging the sleeve means to slidewith said plunger within said body only over a preselected nearerportion of the slidable movement of the plunger which is near theshoulder of the internal bore and for disengaging the sleeve means fromsaid plunger over a remaining portion of the slidable movement of saidplunger which is remote from said shoulder; first spring means disposedwithin said body for resiliently biasing said plunger away from saidshoulder; second spring means disposed within said body to resilientlybias said sleeve means with respect to said body for yieldablymaintaining said sleeve means in fixed position of disengagement fromthe plunger during said remaining remote portion of slidable movementthereof; and electrical switch means disposed within said body to beactuated in response To sliding movement of said sleeve means with saidplunger during said preselected nearer portion of the movement thereof.2. Pipetting apparatus as in claim 1 wherein: said plunger includes amanually-actuatable push rod coupled thereto to protrude from the end ofsaid body remote from said shoulder in substantially coaxial alignmentwith said plunger; said body includes substantially diametricallyopposed, laterally extending portions near the end of the body fromwhich said push rod protrudes; and said switch means is supported withina laterally extending portion of the body to be actuated by slidingmovement of said sleeve means within said internal bore of the body. 3.Pipetting apparatus comprising: a body including an internal boretherein having a shoulder located at a selected depth within theinternal bore, the body having a narrowing portion comprising a volumecylinder which is hollowed to form a volume chamber which is axiallyspaced away from said body internal bore and which communicates withsaid internal bore through an axially aligned aperture within the body;sleeve means mounted within said body for slidable movement therewithinin a direction substantially along the axis of said internal bore; aplunger including a volume rod attached thereto mounted within said bodyfor slidable movement therewithin with said plunger slidably movablewithin said internal bore and with said volume rod protruding throughsaid aperture into said volume chamber; coupling means between saidplunger and said sleeve means for engaging the sleeve means to slidewith said plunger within said body only over a preselected nearerportion of the slidable movement of the plunger which is near theshoulder of the internal bore and for disengaging the sleeve means fromsaid plunger over a remaining portion of the slidable movement of saidplunger which is remote from said shoulder; first spring means disposedwithin said body for resiliently biasing said plunger away from saidshoulder; second spring means disposed within said body to resilientlybias said sleeve means with respect to said body for yieldablymaintaining said sleeve means in fixed position of disengagement fromthe plunger during said remaining remote portion of slidable movementthereof; a liquid-holding tip for said apparatus having a taperedinternal bore which communicates with an orifice at the narrow end ofthe tip and with a connection port at the wide end within which thedistal end of the volume cylinder is inserted; said tip includesvolumetric graduations thereon for visually measuring a volume of liquidwithin the region of the internal tapered bore thereof adjacent saidorifice; and the extreme outside lateral dimension of the volumecylinder near the distal end thereof corresponds with the internaldimension of the tapered bore in said tip for sealingly engaging theinternal tapered bore of said tip above and proximate the volumetricgraduation that is representative of said volume rod protruding intosaid volume chamber by the amount of the calibrated portion of slidablemovement of said plunger.
 4. A universal liquid-holding tip adapted toattach to the inlet and discharge ends of pipetting apparatus having enddiameters that are representative of the maximum capacities of thepipetting apparatus, the tip comprising: an elongated vessel having aninternal bore which communicates with and diverges from an orifice atthe narrow end of the vessel and which also communicates with aconnection port at the wide end of the vessel, said elongated vesselhaving volumetric graduations thereon from the orifice end thereofcorresponding substantially to the maximum capacities of pipettingapparatus to be associated therewith; and the divergence of the internalbore providing sealing engagement with the end of associated pipettingapparatus at a depth within the internal bore that substantiallycorresponds with a volumetric graduation for a liquid volume in theregion adjacent the orifice which is not less than the maximum capacityof the associated pipetting apparatus.